The HANDLS study is an epidemiologic, interdisciplinary, longitudinal study of a baseline representative sample of African Americans and whites between 30-64 years of age recruited as a fixed cohort of participants by household screenings from an area probability sample of twelve census segments in Baltimore City. The HANDLS design is an area probability sample of Baltimore based on the 2000 Census. Using this methodology, working with survey statisticians we chose 12 neighborhoods to meet race by SES by age distribution of the prospective cohort because they were likely to yield representative distributions of Baltimore City with sufficient individuals to fill the sampling design based. Within the 13 neighborhoods, housing units were selected with a known non-zero chance of selection. The addresses were screened for individuals who meet the age-gender-race-poverty sample size, and those were chosen to be included in the sample using a probability sampling method. From these probabilities, we can compute weights to adjust for unequal probabilities of selection. These weights will be needed to compute estimates that combine subjects across any of the age-gender-race-poverty group. The poverty status delimiter is 125% poverty based on 125% of the 2004 Health and Human Services Poverty Guidelines. In the initial examination and recruitment study data was collected in two parts. The first part consisted of an in-home interview that included questionnaires about the participants health status, health service utilization, psychosocial factors, nutrition, neighborhood characteristics, and demographics. The second part was collected on the medical research vehicles and included medical history and physical examination, dietary recall, cognitive evaluation, psychophysiology assessments including heart rate variability, arterial thickness, carotid ultrasonography, assessments of muscle strength and bone density, and laboratory measurements (blood chemistries, hematology, and biomaterials). Using mobile medical research vehicles, we visit each census tract for 4 months and we will re-visit every census tract in a 3.5-year cycle. HANDLS completed its baseline examination wave in March 2009 with a final total accrual of 3720 participants. The cohort is comprised of African American (59%) and Whites (41%). Approximately 41% of the cohort reported a household income below the 125% poverty status delimiter. Of those below the 125% poverty delimiter, 13% were white and 28% African American. Of those above the 125% poverty delimiter, 28% were white and 31% African American. The mean age of the sample was 47.7 years at baseline. There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. HANDLS medical examination rate was 75.2% comparable to the 75% examination rate for the National Health and Nutrition Examination Study (NHANES). Wave 3 examinations started in July 2009 and was completed in June 2013 with a show rate of 91%. The Wave 3 protocol in keeping with the longitudinal study design maintained many of the same study domains as the baseline wave 1 examination including: cognition, cardiovascular disease, nutrition, physical performance, psychology, health services, genomics (genetics and epigenetics), and molecular biomarkers of disease. This protocol also included new areas of study particularly focused on renal function, neuroanatomy, financial and health literacy. Wave 4 conducted from September 2013 through July 2017. The Wave 4 protocol included the addition of the EndoPAT as a measure of endothelial dysfunction, longitudinal assessment of carotid intimal thickness as well and the cognitive domain uses measures that are less dependent on literacy to assess executive function. The Home Visit Protocol developed to prevent the bias resulting from missing data from participants who have become home-bound over the course of the study is ongoing. Wave 5 began in September 2017 with new additions to the protocol including sensory testing (olfaction, vision, fundal imaging), microbiome and environmental exposure biomaterial collection and continues evaluating participants on the MRVs as well as in the home. Notable findings this year include results from our continued participation in international genetic consortia, other studies focused on nutrition, biomarkers of mortality, cognition, brain imaging and the biologic outcomes of discrimination. Among the most notable is our work on frailty. Frailty is generally regarded as a clinical syndrome in the elderly associated with increased risk for disability, hospitalization, and mortality. Although a medical condition, frailty is not synonymous with comorbidities or merely the product of age-associated functional declines. Frailty is a risk factor for disability and mortality and is more prevalent among African American (AA) elderly than whites. We examined frailty in economically diverse, African American and white adults to investigate how race, poverty, and frailty are associated with mortality in a middle-aged cohort. Participants were 3564 years old at initial assessment (56% women; 58% AA). Frailty was assessed using a modified FRAIL scale of fatigue, resistance, ambulation, illness and weight loss, and compared with difficulties in physical functioning and daily activities. Frailty prevalence was calculated across race and age groups, and associations with survival were assessed by Cox Regression. Approximately, 11% of participants were categorized as frail; 36% as pre-frail; 53% as not frail. For those aged 4554, a higher proportion of whites (13%) than AAs (8%) were frail; while the proportions were similar for those 5564 (14%,16%). Frailty was associated with overall survival with an average follow-up of 6.6 years, independent of race, sex and poverty status (HR = 2.30; 95%CI 1.673.18). In this sample of economically and racially diverse older adults, the known association of frailty prevalence and age differed across race with whites having higher prevalence at younger ages. Frailty was associated with survival beyond the risk factors of race and poverty status in this middle-aged group. Early recognition of frailty at these younger ages may provide an effective method for preventing or delaying disabilities. Our data support the notion that frailty is not just a geriatric syndrome but a continuum of signs and symptoms that emerge as early or perhaps earlier than mid-life. The previously recognized higher prevalence of frailty in African Americans may only hold for older ages or be moderated by economic conditions. The FRAIL scale was significantly associated with survival in this cohort of older adults, independent of sex, race and poverty status. Recognition of frailty and pre-frailty before the traditional geriatric age may prevent disability and extend life expectancy in vulnerable groups. This work illustrates that health disparities are important to consider in minority as well as non-minority populations. The finding that middle-aged whites had a higher incidence of frailty in this urban cohort dovetails with the recently reported rising morbidity and mortality rates and stagnation or decrements in life expectancy data for middle aged whites in America.